Various preparations have heretofore been proposed for the treatment of male pattern baldness. It is also a matter of common knowledge, however, that none of the so-called "hair growth formulae" have proven to be very efficacious.
In contrast to most epithelial structures, the hair follicle does not grow continuously throughout its life, but passes through a cycle called the pilar cycle. The pilar cycle comprises essentially three phases--namely, the anagen or growth phase during which hair is produced, normally lasting about three to seven years; the catagen phase when growth stops and the follicle atrophies, lasting about three to four weeks; and the telogen phase, which is a rest period for the follicle during which the hair progressively separates and finally falls out, and normally lasting about three to four months. Normally 80 to 95 percent of the follicles are in the anagen phase, less than 1 percent being in the catagen phase, and the rest being in the telogen phase. Whereas the telogen phase hair is uniform in diameter with a slightly bulbous, non-pigmented root, the anagen phase hair has a large colored bulb at its root.
Alopecia results when the pilar cycle is disturbed, resulting in excessive hair loss. The most frequent phenomenon is a shortening of the hair growth phase due to cessation of cell proliferation. This results in an early onset of the catagen phase, and consequently a large number of hairs in the telogen phase during which the follicles are detached from the dermal papillae, and the hairs fall out. This shortening of the growth or anagen phase of the pilar cycle may have different origins, among which are very diverse pathological origins such as febrile conditions, mental stresses, hormonal problems (such as androgenetic alopecia due to male hormones) and secondary effects of drugs. Alopecia may also be due to age and to a slowing down of mitotic activity. This dysfunction of the biological mechanism of hair growth leading to alopecia may be regarded as a disease. While there are other causes of alopecia such as greasy or oily scalp due to seborrhea and the dandruff accompanying it, the present invention is not directed to treating these extraneous causes of alopecia, but rather to treating the organic dysfunction of the hair follicle.
Minoxidil, a potent antihypertensive, is well known in the literature as a hair growth promoting agent (see U.S. Pat. Nos. 3,461,461; 3,973,016; and 3,464,987). However, it has many undesirable systemic side effects. When the topical compound is absorbed, the systemic side effects include fluid retention, tachycardia, dyspnoea, gynaecomastia, fatigue, nausea and cardiotoxicity.
There is presently a search for analogs, derivatives or other compounds of the minoxidil type which would still possess hair growth activity without the undesirable systemic effects associated with minoxidil. My prior published PCT patent applications Ser. No. US85/00556 (WO85/04577) and US85/01329 (WO86/00616) describe certain pyrimidine oxides (oxamates and carbamates) which are similar to minoxidil and have been found to be useful in hair growth promotion.